(3-hydroxyphenyl)boronic Acid → (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(3'-hydroxybiphenyl-3-yl)azetidin-2-one

HRID 2252434Notes

Reaction equation

HRID 2252434 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:8]2[N:11]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[C:10](=[O:19])[C@@H:9]2[CH2:20][CH2:21][C@@H:22]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[OH:23])[CH:5]=[CH:6][CH:7]=1.[OH:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1>>[F:18][C:15]1[CH:16]=[CH:17][C:12]([N:11]2[C@H:8]([C:4]3[CH:3]=[C:2]([C:36]4[CH:35]=[CH:34][CH:33]=[C:32]([OH:31])[CH:37]=4)[CH:7]=[CH:6][CH:5]=3)[C@@H:9]([CH2:20][CH2:21][C@@H:22]([C:24]3[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=3)[OH:23])[C:10]2=[O:19])=[CH:13][CH:14]=1

Participants

3

Reactant 2

HCID 2734359(3-hydroxyphenyl)boronic AcidHCID 59643931HCID 59643931, compound

Product 1

HCID 59643922(3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(3'-hydroxybiphenyl-3-yl)azetidin-2-oneYield 45%

Procedure

(3R,4S)-4-(3-Bromophenyl)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one (43 mg, 0.091 mmol) was coupled with 3-hydroxyphenyl boronic acid (18 mg, 0.13 mmol) under standard Suzuki conditions illustrated by Example 42. Purified by chromatography (silica gel, 10% to 90% ethyl acetate-hexane) to afford (3R,4S)-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(3′-hydroxybiphenyl-3-yl)azetidin-2-one (19.7 mg, 45% yield); Rf 0.30 (1:1 ethyl acetate-hexane); 1H NMR (300 MHz, CDCl3) δ 7.57-7.40 (m, 3H), 7.34-7.22 (m, 6H), 7.10 (ddd, 7.7, 1.6, 0.9 Hz 1H), 7.04-6.90 (m, 5H), 6.84 (ddd, J=8.2, 2.6, 0.9 Hz, 1H), 5.10 (br s, 1H), 4.72 (t, J=5.9 Hz, 1H), 4.67 (d, J=2.4 Hz, 1H), 3.16 (ddd, J=5.0, 2.6, 2.4 Hz, 1H), 2.26 (br s, 1H), 2.08-1.88 (m, 4H) ppm.

Workup

  1. customPurified by chromatography (silica gel, 10% to 90% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-99153b582b024f4ea98d0e42856b4b69
Source dataset
uspto-grants-2008_01
Patent number
US07320972B2

Reaction notes

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